Benz anthracene 5,6-diol

Slaga, T.J. et al., Carcinogenicity and mutagenicity of benz(a)anthracene diols and diol-epoxides. Cancer Res., 38, 1699, 1978. 

Methods for the synthesis of the biologically active dihydrodiol and diol epoxide metabolites of both carcinogenic and noncarcinogenic polycyclic aromatic hydrocarbons are reviewed. Four general synthetic routes to the trans-dihydrodiol precursors of the bay region anti and syn diol epoxide derivatives have been developed. Syntheses of the oxidized metabolites of the following hydrocarbons via these methods are described benzo(a)pyrene, benz(a)anthracene, benzo-(e)pyrene, dibenz(a,h)anthracene, triphenylene, phen-anthrene, anthracene, chrysene, benzo(c)phenanthrene, dibenzo(a,i)pyrene, dibenzo(a,h)pyrene, 7-methyl-benz(a)anthracene, 7,12-dimethylbenz(a)anthracene, 3-methylcholanthrene, 5-methylchrysene, fluoranthene, benzo(b)fluoranthene, benzo(j)fluoranthene, benzo(k)-fluoranthene, and dibenzo(a,e)fluoranthene. 

Our understanding of the importance of steric factors was initiated by structure determinations by X-ray diffraction techniques of two trans-diols of benz[a]anthracene (89), XVI and XVII, shown in Figure 12. The crystal structures showed diequatorial... 

Figure 12. The structures of two trans diols of benz[a]anthracene showing the diequatorial conformation of the unhindered 10,11-diol and the diaxial conformation of the hindered 1,2-diol. These trends persist in solution where the 10,11-diol exists as an equilibrium of 30% axial and 70% equatorial conformers (that is, the ring is flexible) on the other hand the 1,2-diol is 100% diaxial even in solution. If the 1-hydroxyl group were equatorial it would "bump" into the hydrogen atom on Cl2.

The carcinogenicity of PAH with relativelyTigh IP, such as benzo[c]phenanthrene, benz[a]anthracene, chrysene, 5-methyl chrysene and dibenz[a,h]anthracene (Table I), can be related to the formation of bay-region diol epoxides catalyzed by monooxygenase enzymes (j>). However, the most potent carcinogenic PAH have IP < ca. 7.35 eV. 

Even the 1,2-dihydrodiol derivatives of polycyclic aromatic hydrocarbons are converted to the corresponding epoxydiols with MCPBA. The reaction is stereoselective only in some cases. The trans-dihydrodiols (6) give the antiepoxide (7), whereas the cfs-dihydrodiols (8) give a mixture of anti- (9) and syn-epoxy compounds (10). The anti- and syn-diol epoxides of benz[a]anthracene and benzo[a]pyrene have been prepared by this method.10... 

The syn- and anfi-diol epoxides of benz[a] anthracene and benzo[a] pyrene have been prepared from dihydroarenes by sequential Prevost reaction with silver benzoate-iodine, dehydrogenation, methanolysis, and epoxidation, e.g.,... 

Weems, H., Mushtaq, M., Fu, P., and Yang, S., Direct separation of non-k-region monool and diol enantiomers of phenanthrene, benz[a] anthracene, and chrysene by high-performance liquid chromatography with chiral stationary phases, J. Chromatogr., 371, 211, 1986. 

Analytical Properties Resolution of several enantiomers of polycyclic aromatic hydrocarbons, for example, chrysene 5,6-epoxide, dibenz[a,h]anthracene 5,6-epoxide, 7-methyl benz[a]anthracene 5,6-epoxide resolution of barbiturates, mephenytoin, benzodiazepinones, and succinimides direct separation of some mono-ol and diol enantiomers of phenanthrene, benz[a]anthrene, and chrysene ionically bonded to silica gel, this phase provides resolution of enantiomers of c/s-dihydroidiols of unsubstituted and methyl- and bromo-substituted benz[a]anthracene derivatives having hydroxyl groups that adopt quasiequatorial-quasiaxial and quasiaxial-quasiequatorial conformation Reference 31-35... 

C18H1202 benz(a)anthracene-3,9-diol 56614-97-2 25.00 1.2112 2 30651 C18H18CIN30 dibenzacepin 1977-10-2 2 2... 

Apart from stereoselective bioactivation, stereoselective bioinactivation may be important too from a toxicological point of view. For instance, in contrast to the basic (a-e), the human near neutral ( i,) and acidic (tt) classes of GSH transferases were efficient in the conjugation of benz[aj-pyrene-7,8-diol-9,10-epoxides and, in particular, the carcinogenic (+)-anti-enantiomer (and other +)-flwh-enantiomers of the b -region diol-epoxides of ber z[a]anthracene and chrysene) (Jernstrom et al 1985 Robertson et al., 1986). 

Levin W, Chang RL, Wood AW, et al. 1984. High stereoselectivity among the optical isomers of the diastereomeric bay-region diol-epoxides of benz(a)anthracene in the expression of tumorigenic activity in murine tumor models. Cancer Res 44 929-933. 

Levin, W Thakker, D.R., Wood, A.W., Chang, R.L., Lehr, R.E., Jerina, D.M., and Conney, A.H. (1978) Evidence that benz[a]anthracene-3,4-diol-l,2-epoxide is an ultimate carcinogen on mouse skin. Cancer Res., 38, 1705-1710. 

Malaveille, C., Kuroki, T., Sims, P., Grover, P.L., and Bartsch, H. (1977) Mutagenicity of isomeric diol-epoxides of benzo[a]pyrene and benz[a] anthracene in S. typhimurium TA98 and TA100 and in V79 Chinese hamster cells. Mutat. Res., 44, 313-326. 

Fig. 5. Detoxification of epoxide-containing carcinogens by GST. The following carcinogens are GST substrates (a) aflatoxin Bj-8,9-epoxide, (b) anti-benzo[a]pyrene-7,8-diol-9,10-oxide, and (c) benz[fl]anthracene-5,6-epoxide.

Robertson, 1. G. C, and JemstrSm, B., The enzymatic conjugation of glutathione with bay-region diol-epoxides of benzo(a)pyFene, benz(a)anthracene and chrysene. Carcinogenesis (London) 7, 1633-1636 (1986). 

Abbreviations PAH, polycyclic aromatic hydrocarbon DE, diol epoxide PAHDE, polycyclic aromatic hydrocarbon diol epoxide PAHTC, polycyclic aromatic hydrocarbon triol carbocation TC, triol carbocation BaP, benzo[a]pyrene BeP, benzo[e]pyrene BA, benz[a]anthracene DBA, dibenz[a,h]anthracene BcPh, benzo[c)phenanthrene Ch, chrysene MCh, methylchrysene MBA, 7-methyl benz[a]anthracene DMBA, 7,12-dimethyl benz[a]anthracene EBA, 7-ethyl benz[a]anthracene DB(a,l)P, dibenzo[a,l]pyrene MSCR, mechanism-based structure-carcinogenicity relationship PMO, Perturbational molecular orbital method dA, deoxyadenosine dC, deoxycytosine dG, deoxyguanosine MOS, monoxygenase enzyme system EH, epoxide hydrolase enzyme system N2(G), exocyclic nitrogen of guanine C, electrophilic centre of PAHTC K, intercalation constant CD, circular dichroism LD, linear dichroism. 

For example, polyclonal antibody 29.(12) obtained from animals immunized with BPDE-I-DNA, recognizes DNA modified by chrysene-1,2-diol-3,4-epoxide more efficiently (50 inhibition at 18 fmol) than it recognizes BPDE-I-DNA (50 inhibition at 30 fmol). This antibody also binds to DNA modified by benz(a)anthracene-8,9-diol-10,11-epoxide (50 Inhibition at 42 fmol) and 3,4-diol-l,2-epoxide (50 inhibition at 114 fmol). These results indicate that multiple adducts may be detected by the ELISA. Since humans are exposed to BP in complex mixtures containing a number of other PAHs, a nuBd>er of different adducts may be present. The Identity of the adducts cannot be determined and thus absolute quantitation of abducts is not possible. However, since a number of PAHs in addition to BP are... 

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